Deciphering the Oncogenic Landscape of Hepatocytes Through Integrated Single‐Nucleus and Bulk RNA‐Seq of Hepatocellular Carcinoma
Source abstract
Abstract
Abstract Hepatocellular carcinoma (HCC) is a major cause of cancer‐related mortality, while the hepatocyte mechanisms driving oncogenesis remains poorly understood. In this study, single‐nucleus RNA sequencing of samples from 22 HCC patients revealed 10 distinct hepatocyte subtypes, including beneficial Hep0, predominantly malignant Hep2, and immunosuppressive Hep9. These subtypes were strongly associated with patient prognosis, confirmed in TCGA‐LIHC and Fudan HCC cohorts through hepatocyte composition deconvolution. A quantile‐based scoring method is developed to integrate data from 29 public HCC datasets, creating a Quantile Distribution Model (QDM) with excellent diagnostic accuracy (Area Under the Curve, AUC = 0.968‐0.982). QDM was employed to screen potential biomarkers, revealing that PDE7B functions as a key gene whose suppression promotes HCC progression. Guided by the genes specific to Hep0/2/9 subtypes, HCC is categorized into metabolic, inflammatory, and matrix classes, which are distinguishable in gene mutation frequencies, survival times, enriched pathways, and immune infiltration. Meanwhile, the sensitive drugs of the three HCC classes are identified, namely ouabain, teniposide, and TG‐101348. This study presents the largest single‐cell hepatocyte dataset to date, offering transformative insights into hepatocarcinogenesis and a comprehensive framework for advancing HCC diagnostics, prognostics, and personalized treatment strategies.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Ferroptosis and cancer prognosis · MicroRNA in disease regulation · Hepatitis C virus research
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Biochemistry and Molecular Biology School of Basic Medical Sciences Southern Medical University and Guangdong Provincial Key Laboratory of Single Cell Technology and Application Guangzhou 510515 China
Precision Regenerative Medicine Research Centre Medical Science Division and State Key Laboratory of Quality Research in Chinese Medicine Macau University of Science and Technology Macao 999078 China
College of Life Sciences Shihezi University Shihezi Xinjiang 832003 China
Clinical Biobank Center Microbiome Medicine Center Department of Laboratory Medicine Guangdong Provincial Clinical Research Center for Laboratory Medicine Zhujiang Hospital Southern Medical University Guangzhou 510280 China
Department of Hepatobiliary Surgery I General Surgery Center and Guangdong Provincial Clinical and Engineering Center of Digital Medicine Zhujiang Hospital Southern Medical University Guangzhou 510280 China
Department of Psychiatry Yale University School of Medicine New Haven CT 06510 USA
Division of Hepatobiliopancreatic Surgery Department of General Surgery Nanfang Hospital Southern Medical University Guangzhou Guangdong 510515 China
Key Laboratory of Infectious Diseases Research in South China (China Ministry Education) Southern Medical University Guangzhou Guangdong 510515 China
Funding
National Natural Science Foundation of China
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